The High Throughput Screening (HTS) and Chemical Synthesis (CS) Shared Resource provides state-ofthe- art capability for Vanderbilt-lngram Cancer Center (VICC) researchers to harness the power of HTS/CS to support target discovery, pathway mapping, chemical tool discovery, and exploratory preclinical drug discovery research. HTS/CS includes a chemical library of >170,0000 small molecules, advanced liquid handling, and a broad array of signal detecfion modalifies enabling researchers to address quesfions spanning from protein-protein interactions in purified cell-free systems to colony formation and morphology assays using automated imaging. The facility has the capability of addressing all commonly used opfical techniques (fluorescence, luminscense, kinefic imaging, high-content imaging, scinfillation proximity, refractive index spectroscopy (Corning Epic), automated electrophysiology, and very shortly in collaboration with Stephen Fesik, Ph.D. fragment-based NMR approaches). The complementary CS resource provides an ability to apply advanced chemical synthesis and medicinal chemistry methodologies including solution-phase parallel synthesis, microwave assisted catalysis, automated mass-directed purification, and both chiral synthesis and purificafion resources. HTS/CS employs a highly trained staff of HTS experts who work directly with Vanderbilt investigators to develop, implement, and interpret HTS. This team works hand-in-hand with the team in the CS facility to help investigators extract maximum value from the shared resource by providing a mechanism to use medicinal chemistry techniques to understand, improve, and ufilize HTS hits. David Weaver, Ph.D., directs the HTS component and Alex Waterson, Ph.D., directs the CS portion.